肾移植术后停用环孢素的安全性研究(附42例报告)

Safety evaluation of ciclosporin withdrawal after renal transplantation:42 cases report

目的探讨肾移植受者术后停用环孢素(CsA)的安全性及停用的时机。方法 42例首次接受尸体供肾肾移植患者,术后早期曾采用含CsA的三联免疫抑制方案治疗,停用CsA后改用泼尼松+硫唑嘌呤二联免疫抑制方案4例,改用泼尼松+MMF二联免疫抑制方案38例。根据停药原因分为两组,A组20例患者,包括因移植肾功能减退、蛋白尿停用CsA患者14例、严重肝损害保守治疗无效停用CsA患者4例、不能耐受CsA其他不良反应停用CsA患者2例;B组22例患者肾功能稳定、正常,无CsA导致的不良反应,主动要求或因经济原因停用CsA。另按术后不同时间停用CsA分为两组,术后1年内停用CsA组(16例)与术后1年后停用CsA组(26例)。所有患者均采用逐步停药方法,每周或每2周减少CsA25mg/d,直至完全停药;同时,MMF在原剂量基础上增加0.25～0.50g/d。所有患者均随访超过1年,比较A、B两组患者停用CsA前后的血清肌酐(Scr)变化,并了解肝损害及其他不良反应的发生情况;比较术后不同时间停用CsA患者的排斥反应发生率。结果 A组20例患者在随访期间均未恢复应用CsA,其因CsA导致的肝损害及其他不良反应均有所好转。B组22例患者中,9例在随访期间恢复CsA应用,其中因Scr缓慢上升6例、发生排斥反应1例,患者要求恢复使用2例。A组患者停用CsA前的Scr为(124±30)μmol/L,停用CsA1年后的Scr为(108±12)μmol/L;B组相应为(81±5)μmol/L、(68±4)μmol/L。术后1年内停用CsA组患者的排斥反应发生率明显高于术后1年后停用CsA组的排斥反应发生率(19%比8%,P<0.05)。结论对因使用CsA出现移植肾功能减退、蛋白尿或严重不良反应的患者,在排除移植物排斥的前提下,可逐步停用CsA和(或)相应增加其他免疫抑制药。对于肾功能稳定,未出现CsA不良反应的患者,还是以小剂量CsA维持治疗为妥。CsA的停用时机以肾移植术后1年以上为宜,过早停用CsA会增加排斥反应发生率。

Objective To investigate the safety and timing of ciclosporin （CsA） withdrawal in renal transplant recipients. Methods The data were collected from 42 patients who received primary renal transplantation. All of patients received CsA-based triple immunosuppression therapy after renal transplantation. Dual regimen of prednison ＋ azathioprine was used in 4 cases after withdrawal of CsA and prednison ＋ mycophenolate mofetil （MMF） in 38 cases. According to the withdrawal reasons, the patients were divided into two groups. Group A（ n = 20）included 14 cases with deteriorating renal function and proteinuria, 4 cases with serious liver injury after failure of conservative treatment and 2 cases with other unbearable side-effect of CsA. Group B （n = 22） included 22 patients with stable renal function and no untoward effects of CsA who requested withdrawal of CsA initiatively for economic reasons. According to the withdrawal time, the patients were divided into 2 groups： one group including 16 cases who had CsA withdrawal in 1 year after transplantation and the other group in-cluding 26 cases who had CsA withdrawal over 1 year after transplantation. All of the patients reduced CsA gradually with an amount of 25 mg/d every week or two weeks until total withdrawal, while MMF was increased by 0.25- 0. 50 g/d on the basis of primary dosage. All patients had been followed up for more than 1 year. Serum ereatinine （Scr）, liver function and other untoward effects were compared between Group A and Group B before and after CsA withdrawal. The rejection incidence was compared between patients with different withdrawal time. Results During the follow-up period, all of 20 patients in Group A didn＇ t go back to CsA and the liver injury caused by CsA or other untoward effects were improved. Among 22 patients in Group B, 9 patients went back to CsA. Six of them suffered gradually increased Scr, one developed rejection and two re- quested to reapply CsA. The Scr level of Group A was （ 124± 30） Ixmol/L before CsA withdrawl, and （ 108 ± 12）μmol/L 1 year after that. In Group B, the Scr levels were （81 ±5） μmol/L and （68 ±4）μmol/L re- spectively before and after CsA withdrawl. The incidence of rejection in the group of CsA withdrawal in 1 year after transplantation was significantly higher than that of CsA withdrawal over I year after transplantation （ 19 % vs 8 %, P 〈 0. 05） . Conclusion For patients with renal hypofunction, proteinuria or other serious untoward effects, CsA can be stopped gradually and other immunosuppressive drug can be added on the premise of no graft rejection. It is advisable to keep low-dose CsA use for patients with stable renal function. The suitable timing of CsA withdrawal is over 1 year after transplantation because CsA withdrawal too early can increase the incidence of rejection.